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Universität Hamburg

Synthesis and Characterization of

Photocleavable Polymers and Block Copolymers

Dissertation

Zur Erlangung des akademischen Grades

eines Doktors der Naturwissenschaften

-Dr. rer. nat-

des Fachbereichs Chemie der Universität Hamburg

von

HUI ZHAO

Hamburg

2013

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Die vorliegende Arbeit wurde unter der Betreuung von Prof. Dr. Patrick Theato in der Zeit vom Mai

2010 bis April 2013 am Institut für Organische Chemie der Johannes Gutenberg-Universität Mainz, am

Polymer Science and Engineering Department der University of Massachusetts, Amherst und am Institut

für Technische und Makromolekulare Chemie der Universität Hamburg angefertigt.

Erster Gutachter: Prof. Dr. Patrick Theato

Zweiter Gutachter: Professor Dr. Malte Brasholz Datum der Disputation: 07.06.2013

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Contents

Abbreviations 2

1. Introduction 3

Polymers and block copolymers 5

RAFT polymerization 7

Polymeric activated ester 9

o-Nitrobenzyl alcohol derivatives in polymer and materials science 11

2. Scope and objectives 19

3. Results and discussion 20

3. 1 Functionalized Nanoporous Thin Films and Fibers from Photocleavable Block Copolymers Featuring Activated Esters 21

3.2 Photocleavable Triblock Copolymers Featuring Activated Ester Middle Blocks: Synthesis and Application as Naoporous Thin Film Templates 33

3. 3 Photolabile Amine Semitelechelic Polymer for Light-induced Macromolecular Conjugation 43

4. Overview of Results 55

5. Summary 59

6. Experimental Part 61

7. References and notes 69

8. Appendix (published work) 76

8. 1 Highly-ordered Nanoporous Thin Film from Photocleavable Block Copolymer 76

8. 2 Copolymers Featuring Pentafluorophenyl Ester and Photolabile Amine Units: Synthesis and Application as Reactive Photopatterns 100

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10.Acknowledgements 116

Additional information (Chemicals, Lebenslauf, Erklärung über frühere Promotionsversuche, Eidesstattlicher Erklärung) 117-125

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Abbreviations

AIBN azobisisobutyronitrile ATR attenuated total reflection

ATRP atom transfer radical polymerization CTA chain transfer agent

DLS dynamic light scattering DMF dimethylformamide DMSO dimethylsulfoxide FT fourier transform

GPC gel permeation chromatography IR infrared radiation

LCST lower critical solution temperature Mn molecular weight (number average) Mw molecular weight (weight average) NMP nitroxide mediated polymerization NMR nuclear magnetic resonance ONB o-nitrobenzyl

POEGMA poly(oligo(ethylene glycol) methyl ether methacrylate) PEG poly(ethylene glycol)

PEO poly(ethylene oxide) PFP pentafluorophenol

PNIPAM poly(N-isopropyl acrylamide) PPFPA poly(pentafluorophenyl acrylate)

RAFT reversible addition-fragmentation chain transfer TEM transmission electron microscopy

UV ultra-violet (light) Vis visible (light)

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1. Introduction

1.1 Polymers and block copolymers

Polymers have a very close relationship with our normal life, for example, the proteins and starch in

food are polymers. They can be classified as natural and synthetic polymers based on their sources. A

polymer has high relative molecular mass and polydispersity. From the view of chemistry, a polymer is

a compound that contains repeating units created through polymerization. The repeating units in

polymers are called monomers. Homopolymer is a polymer derived from one monomer while copolymer

from two (or more) monomeric species. Copolymers are classified as alternating, period, statistical or

block copolymers based on the manner in which the copolymers are connected together. Among the

categories of copolymers, block copolymers consisting of chemically distinct polymers linked by a

covalent bond have attracted increasing attention for their ability to self-assemble into a variety of

ordered nanostructures.

1.2 Molecular structure of block copolymers

The molecular structures of a block copolymer (BCP) can be classified as linear AB, linear ABA, linear

ABC and star ABC, depending upon the number and type of blocks and the manner in which the blocks

are connected together (Figure 1.1a). The molecular structures of BCPs are not limited to the

aforementioned 4 types. In a recent review by Bates and coworkers, linear multiblock and circle block

copolymers were also reported. 1 The simplest type is the linear AB diblock copolymer shown in Figure

1.1a, in which a homopolymer A is covalently linked to a homopolymer chain B. A linear AB diblock

copolymer is usually prepared by two routes: a) the repeated addition of monomers of B to the end of the

previously synthesized chain of poly(A), b) conjugation or coupling reaction (eg.“click” reaction)

between poly(A) and poly(B). Linear or star triblock can be prepared by similarly synthetic routes used

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Figure 1.1 Block Copolymer Architectures. (a) Linear AB diblock copolymer. (b) Linear ABA triblock copolymer. (c) Linear ABC triblock copolymer. (d) Star ABC triblock copolymer

1.3 Diblock Copolymer Morphologies

As illustrated in Figure 1.2, linear AB diblock copolymers can form several different morphologies

(spherical, cylinder, gyroid and lamellar) and many years of theoretical and experimental work were

required to understand their phase behavior.1 To a good approximation, AB diblock copolymers have a "universal" phase diagram in which the equilibrium structure is determined by the block volume fraction

fA and block-block interaction parameterABN while segment asymmetry (PA≠PB), molecular weight and

polydispersity shift the boundaries between phases.

Figure 1.2 Diblock Copolymer Morphologies. Depending on the volume fraction of A (fA) and interaction

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For volume fractions between those cylinder and lamellar structures, the double gyroid (G) network structure can form for some values of the block-block interaction parameterABN.

2

1.4 Nanoporous Thin Films from BCPs

Block copolymer lithography employing nanoporous thin films has received increasing attention as a

road to enable the development of future technologies. Nanoporous thin films can be fabricated from a

AB block copolymer thin films with aligned nanoscopic B cylinders in a matrix A. Figure 1.3 shows a

visual schematic representation of this process. The blocks A and B should have enough contrast

chemical or physical condition so that selective removal of B can be achieved. Further, the

nonremovable block A should have a big modulus (it normally has high Tg, Tm or crosslinked structures),

making the pores structure in the films stable after removing the block B. Diverse methods have been

developed for the selective removal of one domain, such as chemical etching, ozonolysis, and UV

degradation. 2, 3

Figure 1.3 Schematic representation of the formation of nanoporous polymeric materials from ordered block copolymers.3

Here, Polystyrene-block-poly(methyl)methlactylate (PS-b-PMMA) was used as an example to

illustrate how to prepare nanoporous thin films from degradable BCPs. As shown in Figure 1.4, once

well-ordered films of PS-b-PMMA were obtained after substrate modification, spincoating, and thermal

annealing, the nanoporous templates can be prepared by removing the PMMA block by deep UV

irradiation (= 254 nm) under vacuum. The resulting pore size of the nanoporous templates can be simply tuned by varying the molecular weight of PS-b-PMMA BCPs. For cylindrical PS-b-PMMA, Xu

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et al. demonstrated that the pore size can be tuned from 14 to 50 nm by changing molecular weight of

PS-b-PMMA.4

Figure 1.4 a) Schematics to prepare the nanoporous template from PS-b-PMMA thin film. The surface is first treated with PS-r-PMMA random copolymers, either having hydroxyl-terminated or crosslinkable group, and then PS-b-PMMA thin film is spin casted, and thermally annealed. Finally, the PMMA block is removed by UV irradiation to generate the nanoporous PS template.5

Table 1. General degradation methods to fabricate nanoporous thin films.

Degradable polymers in BCPs methods references

PB or PI O3, UV, RIE 6

PCLor PLA basic or acidic solution 7

PDMS anhydrous HF 8

PMMA UV or thermal decomposition 4, 9

PPO decomposition 10

PS Fuming nitric acid 11

PMS UV 12

PtBA orPtBMA acid condition 13

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The recent emergence of techniques for implementing controlled free radical polymerization (CRP)

has provided a new set of tools that allow very precise control over the polymerization process. The

living radical polymerization also provides the chance to make precise and complicated polymer

structures for potential applications in many fields, such as self-assembly,14 crystallization,15 and biomaterials.16

Controlled or living free radical polymerization techniques normally include nitroxide mediated

polymerization (NMP), atom transfer radical polymerization (ATRP) and the reversible

addition-fragmentation chain transfer (RAFT) polymerization. The NMP technique was devised in the early

1980s. This polymerization method has been exploited extensively for the synthesis of homopolymers

(especially for polystyrene) and block copolymers with a narrow molecular weight distribution. ATRP

was discovered by Matyjaszewski17a and Sawamoto17bindependently in 1995. ATRP is a versatile polymerization technique. However, it requires unconventional initiating systems, such as copper salts,

which demonstrate poor compatibility to the polymerization media. Further, the use of transition metals

in ATRP poses a potential problem toward biological uses of the resulting polymers. Substantial

advances have been made to address this and other issues. RAFT, discovered at the Commonwealth

Scientific and Industrial Research Organisation (CSIRO) in 1998, is probably the most widely used

process for the commercial production of high-molecular weight polymers.18 RAFT polymerization uses thiocarbonylthio compounds, such as dithioesters, thiocarbamates, and xanthates, to mediate the

polymerization via a reversible chain-transfer process. As with other controlled radical polymerization

techniques, RAFT polymerizations can be performed with conditions to favor low polydispersity

indices and a pre-chosen molecular weight. RAFT polymerization can be used to design polymers of

complex architectures, such as linear block copolymers, comb-like, star, brush polymers and dendrimers.

The RAFT polymerization mechanism is illustrated in Figure 1.5. There are a number of steps in a

RAFT polymerization: initiation, reversible chain transfer, re-initiation, chain equilibrium, and

termination.19 In the initiation step, the reaction is started by a free-radical source, which may be a decomposing radical initiator such as AIBN. In the example in Figure 1.5, the initiator decomposes to

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form two fragments (I•) which react with monomer molecules to yield a propagating (i.e. growing) polymeric radical, denoted Pn•. In the next step, reversible chain transfer, a polymeric radical with n

monomer units (Pn) reacts with the RAFT agent (S=C(Z)S-R) to form a RAFT adduct radical. This

adduct may undergo a fragmentation reaction in either direction to yield either the starting species or a

radical (R•) and a polymeric RAFT agent (S=C(Z)S-Pn). This is a reversible step in which the

intermediate RAFT adduct radical is capable of losing either the R group (R•) or the polymeric species (Pn•). The losing group (R•) from “reversible chain transfer” step will initiate the monomers and yield a

polymeric radical Pm•, this step is called “reinitiation”. “Chain equilibriation” is the most important part in the RAFT process,in which, by a process of rapid interchange, the present radicals (and hence

opportunities for polymer chain growth) are "shared" among all species that have not yet undergone

termination (Pn• and S=C(Z)S-Pn). Ideally the radicals are shared equally, causing chains to have equal

opportunities for growth and a narrow PDI. The last step, is “termination”. Chains in their active form

react via a process known as bi-radical termination to form chains that cannot react further, know as

dead polymer. In ideal conditions, the RAFT adduct radical does not undergo termination reactions.

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1.6 Polymeric Activated Ester

Figure 1.6 Schematic principle of a controlled polymerization of activated ester monomers followed by a controlled functionalization via a polymer analogous reaction.

Figure 1.7 Polymeric activated ester-amine chemistry.

The synthesis of functional and well-defined polymers is still a challenge in polymer science.

Functional polymers can be obtained from polymerization of functional monomers. In some case,

protection of functional groups has to be carried out because the monomers cannot be polymerized

directly. However, the subsequent deprotection step may not necessarily proceed to completion. The

direct polymerization of monomers bearing functional groups is clearly a more favored strategy.

Traditional living techniques, such as anionic polymerization only offer very limited possibilities for the

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polymerization can tolerate many functional groups. However, there is still a broad range of

functionalities that cannot be introduced into apolymer by direct polymerization. Postpolymerization

modification (also called polymer analogous reaction) has drawn increasing attention for its powerful

behavior in the synthesis of functional polymers. The synthesis of functional polymers through a

polymer analogous reaction is divided into two steps: a) polymerization of monomers with functional

groups b) quantitative conversion of the functional group in the synthesized polymers into a broad range

of other functional groups (see Figure 1.6). Consequently, polymer analogous reaction allows access to

functional polymers that cannot be prepared by direct polymerization of the corresponding functional

monomer.

The chemistry of activated esters and amines has found a broad application in peptide chemistry over

many years. The synthesis and post-polymerization modification of active ester polymers was pioneered

by Ferruti and Ringsdorf in the 1970s.20 The reaction of active ester polymers with amines is probably the most frequently used post-polymerization modification strategy. Amines (Figure 1.7) are most often

used for the post-polymerization modification of active ester polymers since they can react selectively

even in the presence of weaker nucleophiles, such as alcohols. In recent years, activated esters polymers

have found broad applications in polymer chemistry as well as in material- and life science.

Figure 1.8 Monomers featuring activated esters for controlled radical polymerization.

Monomers featuring activated esters for controlled radical polymerization can be summarized in

Figure 1.8. The vinyl monomers for CRP include acrylate, methyl acrylate and vinyl benzene. The

leaving groups for activated ester-amine chemistry are strong withdrawing electron groups such as

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activated esters, PFP ester has increasing attention for the fact that poly(pentafluorophenyl acrylates)

(PPFPA) and poly(pentafluorophenyl methacrylates) (PPFPMA) have excellent solubility in common

organic solvents. Further, by using 19F NMR spectroscopy it is possible to monitor the reaction of the PFP ester groups. The conversion of PPFPA and PPFPMA activated esters with amines is usually

quantitative and without any side reactions. In contrast to the copper-catalyzed [2+3] Huisgen alkyne-azide cycloaddition (CuAAC) “click” chemistry, the reaction of activated esters with amines has the advantage to proceed without the auxiliary usage of a metal catalyst. This synthetic procedure also occurs under mild

conditions, such as stirring at room temperature.

1.7 o-Nitrobenzyl Alcohol Derivatives in Polymer and Materials Science

$1

O-nitrobenzyl (ONB) alcohol derivatives have gained tremendous attention in the area of synthetic organic chemistry and beyond. First described by Schofield and co-workers,22 the chemistry was not widely recognized until Woodward and co-workers utilized what has become one of the most popular

photolabile protecting groups.23 It is based on the photoisomerization of an o-nitrobenzyl alcohol derivative into a corresponding o-nitrosobenzaldehyde upon irraditation with UV light (Figure 1.9),

simultaneously releasing a free carboxylic acid. This mechanism has been investigated in detail, most

recently by Wirz and co-workers.24

Figure 1.9 Photoisomerization Mechanism of o-Nitrobenzyl Alcohol Derivatives into an o-itrosobenzaldehyde, Releasing a Carboxylic Acid

$1 This part is selected from our recent review paper. Zhao, H. etc. “Ortho-nitrobenzyl alcohol derivatives: Opportunities in Polymer and Materials Science” Macromolecules 2012, 45, 1723–1736. Copyright 2011 American Chemical Society.

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Polymers featuring photolabile groups are the subject of intense research because they allow the

alteration of polymer properties simply by irradiation. The recent years have seen an explosive

utilization of this chemistry and the following section tries to summaries the recent advances in this area

in polymer chemistry. It covers the use of (i) ONB based crosslinkers for photodegradable hydrogels, (ii)

ONB side chain functionalization in (block) copolymers, (iii) ONB side chain functionalization for thin

film patterning, (iv) ONB for selfassembled monolayers, (v) photocleavable block copolymers, and (vi)

photocleavable bioconjugates.

1.7.1 ONB based crosslinkers for photodegradable hydrogels

The first example of model cross-linked networks based on ONB linkers was reported in 2007 by

Torro and co-workers. 25Similarly, Kasko and co-workers combined the efficient light degradable property of ONB esters with the biocompatibility of PEO, resulting in a photocleavable hydrogel (Figure

1.10).26 This laid the foundation to trap living cells in the hydrogels, which may be released upon irradiation with light in a highly controlled manner (Figure 1a). Using two-photon photolithography, 3D

channels for the migration of cells can successfully be obtained (Figure 1.10b). This “smart

hydrogel”takes advantage of ONB-based cross-links and thus opens an exciting application area for hydrogels.27

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Figure 1.10 Chemical structure of a photodegradable hydrogel based on an ONB linker (upper) (redrawn after ref 17) and light-induced migration of entrapped cells (lower)

1.7.2 ONB side chain functionalization (block) copolymers

Light is an intriguing external stimulus; it is efficient and convenient and can be applied in a targeted

and specific manner via a variety of focusing or lithographic techniques. Consequently, light responsive

block copolymer micelles have been explored for entrapping dyes and drugs with the intention of

releasing them at a defined time and location. ONB esters are a good candidate for constructing light

responsive materials since they are efficiently cleavable upon UV exposure. Zhao and co-workers first

reported that ONB functionalization in side chain of amphiphilic BCPs could be used to produce light

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Figure 1.11 Chemical structure and photolysis of ONB-containing amphiphilic block copolymers and their use for photocontrolled drug release.

1.7.3 ONB side chain functionalization thin films patterning

Figure 1.12 Chemical structure of a photosensitive terpolymer and its mechanism for patterning. (Reprinted with permission from ref 29. Copyright 2004 American Chemical Society.)

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It has been reported that polymers prepared by polycondensation of 2-nitro-1,3-xylylenedibromide with

4,4′-isopropylidenediphenol, decomposed upon UV irradiation, suggesting that these materials can be

used for positive-type photoresists.29 Similarly, Lee and co-workers synthesized a polyimide precursor with ONB ester functionalities in the side chains.30 They shew that this polyimide became soluble in basic solution after UV irradiation and thus can be used as positive photoresist. Doh and Irvine designed

a terpolymer poly(onitrobenzyl methacrylate-co-methyl methacrylate-co-(ethylene glycol) methacrylate)

(P(ONBMA-co-MMA-co-EGMA)) to prepare thin film patterns on the micrometer scale. They

demonstrated that for a terpolymer composition of 43 wt % ONBMA, 38 wt % MMA, and 19 wt %

EGMA the exposed areas of a thin film could be dissolved by phosphate-buffered saline after UV

irradiation (see Figure 1.12). 31

1.7.4 ONB for Self-assembled Monolayes to Control Surface Properties

Figure 1.13 (A, B) Photopatterning by UV light to induce hydrophilic and hydrophobic surface patterns inside microchannels. (C, D) Flow profiles of dilute Rhodamine B aqueous solution inside the surface patterned microchannels.32

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Self-assembled monolayers (SAMs) have proven powerful tools to control surface energy and

influence a variety of properties, e.g., adhesion, wetting and flow profiles, or etch resistance. It was

reported by Moore and co-workers that photopatternable SAMs based on ONB chemistry could nicely

direct liquid flow inside microchannels (Figure 1.13).32 Essentially, the ONB-based SAM was employed in a photolithographicand thereby contact free method resulting in patterns of differing surface free energies inside microchannels.

1.7.5 ONB junctions to cleave Block Copolymers

Block copolymers (BCPs) have been studied extensively due to their ability to self-assemble into a

range of well-defined, well ordered structures. In recent years, the interest in block copolymers serving

as nanotechnological templates has resulted in a multitude of research efforts. Block copolymer thin

films with a morphology oriented perpendicular to the substrate are the current focus of many research

groups, with a particular aim of preparing well-ordered, nanoporous thin polymer films.33 Currently, several challenges have to be addressed to overcome the limitations still present in thin block copolymer

films. The first is achieving high lateral order in the morphology, and the second is facile, selective

removal of one phase. Several methods that allow for selective removal of one domain have been

presented in the literature, such as chemical etching, ozonolysis, pH induced hydrolysis, and UV

degradation. In particular, block copolymers with a cleavable junction are interesting since they can be

used as precursors for generating hollow structures after cleavage and selective removal of one of the

blocks. This can have an impact on the formation of hollow micelles and nanoporous polymeric

materials.34As ONB is a well-known photocleavable junction, photocleavable block copolymers can be prepared based on this structure. Kang and Moon are the first to prepare and characterize photocleavable

block copolymer thin films based on ONB (Figure 1.15). 35 They prepared the photocleavable diblock copolymer polystyrene-block-poly-(ethylene oxide) (PS-hν-PEO) by ATRP using an ONB

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functionalized PEO macroinitiator (Figure 10). Recently, Fustin and co-workers developed a more

versatile synthetic route toward photocleavable block copolymers on the basis of an ONB junction.36 As copper(I) is known to be a catalyst for both ATRP and azide−alkyne cycloaddition (CuAAC) click

reaction, they performed ATRP and click chemistry in a one-pot synthetic strategy using an ONB ester

featuring dual functionality to synthesize several photocleavable block copolymers including

PS-hν-PEO, which was used in the work of Kang and Moon (Figure 1.14). Theato, Coughlin, and co-workers

extended this approach by combining RAFT polymerization and a subsequent intermacromolecular

azide−alkyne click reaction, providing more flexibility in the synthesis of photocleavable block

copolymers.37 Highly ordered thin films were prepared, and after photoetching the resulting nanoporous films were used to prepare the first examples of nanostructures from a photocleavable polymer template.

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Figure 1.15 (A) AFM image (1 × 1 μm2) of PS-hν-PEO (23.7-b-5.0 K) films (thickness = 43 nm) spin-coated onto silicon wafers and solvent annealed for 2 h (benzene/water). (B) SEM image of the nanoporous PS thin film resulting from photocleavage and selective solvent removal (methanol/water) of PEO phase. 35

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2 Scope and objectives

The general target of this thesis is to establish a synthetic method to produce block copolymers

featuring photocleavable junctions. Further, to produce highly ordered nanoporous thin films based on

photocleavabale BCPs, the best process conditions will be explored. Finally, the possibility that the

resulting nanoporous thin films are used for highly ordered templates will be studied. The key idea for

nanoporous thin films from photocleavable BCPs is shown in Figure 2.1.

Wash

Figure 2.1 Schematic representation of the self-assembly of photocleavable block copolymers and

the subsequent removal of one domain after UV irradiation.

The synthesis of well-defined polymers with ONB photocleavable groups will be developed utilizing

modern polymerization methods, such as the reversible addition fragmentation chain transfer (RAFT)

polymerization, combination with copper catalyzed azide-alkyne cycloaddition “click” chemistry and

activated ester-amine chemistry.

Besides incorporating the ONB at the junctions between BCPs, ONB can also be as side chains or

end groups in a polymer. Based on activated ester-amine chemistry, well-defined polymers with ONB

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3.1 Functionalized Nanoporous Thin Films and Fibers

from Photocleavable Block Copolymers Featuring

Activated Esters

Introduction

Nanoporous materials have received continuous attention since they find numerous applications,

including as gas storage materials,38 separation materials,39 agents for controlled release of drugs,40 supports for catalysts,41 cell scaffolds, 42 photonic band gap materials,43 filtration-separation membranes,44 and templates for structure replication.45 Among the strategies to produce nanoporous materials, self-assembly of block copolymers (BCPs) has received considerable attention as a promising

platform for "bottom-up" fabrication of nanostructured materials and devices.46 Generally, to fabricate nanoporous thin films, minor domains within the BCP films need to be removed or reconstructed.47 Diverse methods have been developed for the selective removal of one domain in BCP thin films,

including chemical etching,48 ozonolysis,49 and UV degradation.50 However, most of these methods require harsh treatment conditions. Recently, the groups of Moon, Fustin, Coughlin and Theato

developed block copolymers with photocleavable junctions based upon the o-nitrobenzyl ester (ONB).

These investigations have established ONB-based BCPs as a promising platform for the synthesis of highly ordered nanoporous thin films.35-37

Nanoporous materials featuring reactive or functionalized nanoporous materials have attracted increasing interest as they can be tuned easily by incorporating a variety of functional groups into the nanoporous matrix. Hillmyer and coworkers developed an ABC (polystyrene-block-poly(dimethylacrylamide)-block-polylactide) triblock system to fabricate reactive nanoporous thin

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films.52, 53 More recently, amine and carboxylic acid functionalized nanoporous thin films based on photocleavable diblock copolymers were reported by Fustin.51, 54 Most functionalization methods reported to date focus only on the surface modification of pore walls in porous thin films. The functional groups present on the porous thin films were found to be only partially active and react under limited conditions. There is a strong need for versatile synthetic routes toward nanoporous materials that provide possibilities for post-functionalization after removal of one component of the BCP. Herein, we

report the synthesis of photocleavable block copolymers with reactive poly(pentafluorophenyl-(methyl)-acrylate)s (PPFP(M)A) as the major block and PEO as the minor

block. The pentafluorophenyl ester, is known to react with amines under very mild conditions (room temperature and catalyst free) based on activated ester-amine chemistry, yielding the respective functional poly((meth)acrylamide).55 This novel matrix functionality of pentafluorophenyl esters offers a more efficient way to tune the properties of nanoporous structures compared to surface functionalization of pore walls.

Results and Discussion

Synthesis and characterization. In previous reports, we presented polymers featuring

pentafluorophenyl (PFP) esters as promising reactive polymeric precursors for the synthesis of

multifunctional polymers.55 In this paper, we chose perfluorophenyl acrylate (PFPA) and pentafluorophenyl methacrylate (PFPMA) as monomers to serve as a hydrophobic block in the

photocleavable block copolymers. The strong hydrophobicity of PPFP or PPFPMA blocks leads to a

significant incompatibility with the hydrophilic PEO block and, as a result, large non-favorable

Flory-Huggins interactions between the PPFPA/PPFPMA and PEO blocks. We first attempted a RAFT-click

route to synthesize the block copolymer (supporting information, Scheme S1): poly(pentafuorophenyl

(methyl) acrylate) with an alkyne end group was obtained by RAFT polymerization and the PEO block

was then conjugated with the PFP(M)A block using copper-catalyzed [2+3] Huisgen alkyne-azide

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which we attribute to the copper (I) catalyst interfering with the pentafuorophenyl (methyl) acrylate,

leading to hydrolysis of the ester, followed by protonation and coordination of the ligands and copper,

respectively.

Accordingly, we synthesized a macromolecular chain transfer agent (Macro-CTA) for subsequent

RAFT polymerization of PFPA or PFPMA. As shown in Scheme 3.1.1, the Macro-CTA containing an

ONB junction was prepared by a click reaction between and azide-functionalized PEO and

alkyne-functionalized CTA (Scheme 3.1.1, see experimental section for details for Macro-CTA synthesis). The

yield of the Macro-CTA is high (pink powder, yield up to 90%) and CTA end group functionality is over

85% (calculated by 1H NMR, Figure 3.1.1A). This Macro-CTA can be efficiently controlled RAFT polymerization of PFPA and PFPMA monomers. All polymers were fully characterized by FTIR, 1H and

19

F NMR. Take PEO-hv-PPFPMA (P4) as an example: as can be seen from Figure 3.1.1, the proton

resonance 1.0 to 2.8 ppm are assigned to the PPFPMA block while the resonances between 3.3 and 4.5

ppm are assigned to the PEO block. Typical proton resonances (e, f in Figure 3.1.1B) from the ONB junction are also observed. As can be seen from Figure 3.1.1, the proton ratio between the labeled

aromatic protons c:b:d is 1.00:1.98:1.96, which indicates the benzoic dithioester and o-nitrobenzyl ester

groups in the Macro-CTA remained intact after the CuAAC “click” reaction. 19F NMR results also support that we obtained block copolymers containing pentafluorophenyl esters (see Figure 3.1.1C).

Control of the block copolymer dispersity (Ɖ) was not perfect as we expected for a RAFT

polymerization, and the Ɖ values smaller than 1.5 were achieved, which is most likely due to the

nitro-group of ONB functionality. (Figure 1 and Table 1, Mn: 10~32.4k g/mol, Mw/Mn:1.29~1.46). (For further

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Scheme 3.1.1 Synthetic routes to photocleavable BCP featuring activated esters

Table 3.1.1 Synthesis of Photocleavable BCP Featuring Activated Esters via RAFT polymerization using a PEO-based Macro-CTA (Mn,GPC = 7000, Ɖ =1.10, PS standard).

Polymer Monomer Mn (g/mol)

a Ɖa f PEO b P1 PFPA 10 000 1.29 0.33 P2 PFPA 18 800 1.47 0.21 P3 PFPA 23 000 1.41 0.19 P4 PFPMA 25 300 1.31 0.17 P5 PFPMA 28 500 1.40 0.15 P6 PFPMA 32 400 1.46 0.14 a

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PEO

C - 1 8 0 - 1 6 0 - 1 4 0 - 1 2 0 p p m 3 2 3 2 1 B CN S n O O O2N O N N N O 113 O O F F F F F S

f

e,f

e

d

c

b

b

a

O O NO2 O N N N S NC S O 113

a

c

d

PPFPMA

A 1

Figure 3.1.1 1H NMR for Macro-CTA (A) and PEO-hv-PPFPMA (B) in CDCl3. 19

F NMR for PEO-hv-PPFPMA (C) in CDCl3.

The photolysis of the photocleavable block copolymers was investigated by exposing solutions of this

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UV-visible absorption spectrum of P4 changed significantly over the course of irradiation time. The

absorption intensity at 310 nm (associated with the ortho-nitrobenzyl moiety) decreased with increasing

irradiation time, while additional bands appear between 350 and 450 nm due to the formation of the

ortho-nitrosobenzyl functionality.56 The photocleavage of ONB proceeded rapidly under a high intensity 500W UV source, with complete photolysis reached within 15 min. Photocleavage was also confirmed

by GPC, Figure 3.1.2 analysis shows the complete photocleavage of PEO-hv-PPFPMA. After UV

irradiation (1 h), the peak at the elution time associated with the block copolymer becomes two lower

molecular weight peaks, which were assigned to PEO and PPFPMA respectively.

Preparation and functionalization nanoporous thin films.

The strong hydrophobicity of the PPFP or PPFPMA block results in a large Flory-Huggins parameter

( between PPFPA/PPFPMA and PEO, which should result in strong phase-separation. The diblock copolymers P3 and P4 were annealed at 160 oC for 24 hours, followed by small angle X-ray scattering analysis (SAXS) to investigate the phase separated morphologies.

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- 28 - 250 300 350 400 450 500 550 0.0 0.2 0.4 0.6 0.8 NO2 O NO O

=365 nm

Time/min 0 1 3 5 10 15 20

A

bs.

(nm)

A

12 14 16 18 20 PEO-hv-PPFPAMA PEO-hv-PPFPAMA UV

Elution Time (min)

B

Figure 3.1.2 UV spectra (A) (Concentration: 0.02 mg/mL, THF) and GPC trace (B) for PEO-hv-PPFPMA before and after UV in THF.

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- 29 - 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0 50 100 150 200 250 q * q * 4 q * 3 In te n si ty ( a . u .) q (nm-1) PEO-PPFPA (P3, 5k-18k) PEO-PPFPMA (P4, 5k-20k) q *

Figure 3.1.3 SAXS for PEO-hv-PPFPA (P3, 5k-18k) and PEO-hv-PPFPMA (P4, 5k-20k) after thermal annealing at 160 oC 24h. Gray, P3; black, P4.

As shown in Figure 3.1.3, SAXS results show that both samples display phase separation. However,

PEO-hv-PPFPMA featured a better phase separation behavior than PEO-hv-PPFPA: a first order

reflection at q* = 0.117 nm-1 and two higher order reflections at q2 = 0.187 nm-1 (√3 q*) and q3 = 0.229

nm-1 (√4 q*) were observed, indicative of hexagonally packed cylindrical PEO microdomains oriented normal to the film surface. Solvent annealing was performed to further refine the morphology. After

water/THF (0.1 ml/0.2 ml) mixture solvent annealing for 2.5 h at 20 oC, the thin film surface morphologies were analyzed by Atomic Force Microscopy (AFM). As shown in Figure 3.1.4: the

sample P4 showed quasi-hexagonally packed circular microdomains, which are characteristic of PEO

cylindrical microdomains oriented perpendicular to the substrate, while P3 is in disordered state. The

average center-to-center distance of adjacent cylinders in Figure 3.1.4C was calculated to be 50 nm,

which was consistent with SAXS results (53 nm).

The high reactivity of activated esters to amines facilitates the functionalization of these thin films.

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- 30 -

irradiation ( = 365 nm, 6 W) for 12 hours and then immersed in solutions of amines (hexamethylene diamine/cysteamine, molar ratio: 2/1) in methanol to remove the minor PEO block while simultaneously

functionalizing the polymer matrix. The PPFPMA matrix was reacted with two amines; the first a

difunctional amine to crosslink the matrix and the second, cysteamine, introduced thiol moieties, as

shown in Figure 3.1.4. The nanoporous morphology of the thin films remained after UV irradiation,

methanol rinsing and amine modifications (Figure 3.1.4). This is remarkable considering the extensive

post-modification applied to the films. The pore size is around 33 nm, which is similar to that before UV

and methanol treatment (pore size around 35 nm). XPS measurements confirmed successful

post-modification of the thin films. Firstly, the F1s peak at a binding energy of 686 eV (S2 A) from the

pentafluorophenyl ester PFPMA-hv-PEO completely disappeared after post-modification (S2 B);

Moreover, N1s and S2p binding peaks appeared at 402 and 165 eV respectively, which means that the

PFP ester was successfully converted to imide in the thin film. However, XPS is only useful for

diagnosis of surface film layers and may not accurately describe the chemical composition in the bulk

film. Although we do not have conclusive proof that the post-modification was complete throughout the

entire film from XPS results, we speculate the conversion is high, as our previous studies have shown

that thicker (more than 100 nm) PFPA-based polymer films could be converted quantitatively with

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- 31 - A B C D E F NC S n O O NO2 O N N N O 113 O O F F F F F S O H N n H N 3 O H N O S H hv, MeOH wash hexamethylene diamine cysteamine P4 P4-SH

Figure 3.1.4 AFM images for PEO-hv-PPFPA (P3, 18k, A: Height, B: Phase), PEO-hv-PPFPMA (P4, 5k-20k, B: Height, D: Phase) after water/THF annealing 2.5 h, 20oC, and image (E: Height, F: Phase) for PEO-hv-PPFPMA after UV and post-modification treatment with amines. Scale: 2m x 2m (A-D), 1m x 1m (E: Height, F: Phase).

Functionalized nanoporous fibers

Polymer nanofibers have attracted much interest for their varieties of applications, such as

reinforcing component in composite systems, 58templates for preparation of functional nanotubes,59biomedical and filter applications.60 In a previous study, Boerner and coworkers showed

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- 32 -

that the surface of PFP homopolymer nanofibers could be functionalized with suitable bioactive

entities.61 Successful preparation of reactive nanoporous thin films based on PEO-hv-PPFPMA, encouraged us to make reactive and nanoporous fibers from PEO-hv-PPFPMA via electrospinning from

a 1:4 (v:v) DMF/THF solution. As shown in Figure 3.1.5A, the diameter of the fibers ranged from 800

nm to 2 m. After water/THF (0.1 ml/0.2 ml) annealing for 2 h, phase separation was observed by SEM and PEO cylinders were likely oriented parallel to the fiber direction due to the electro-spinning

process.63 Functionalized porous fibers were obtained by a similar procedure as that described above for the fabrication nanoporous thin films; UV irradiation followed by methanol rinsing and the reaction with

an amine solution. In this case, a fluorescent amine, 4-nitro-7-(piperazin-1-yl)benzo[c][1,2,5]oxadiazole

(NBD), was used for functionalization. As shown in SEM images Figure 3.1.5 (C and D), the fiber

structures remained completely intact and the surfaces displayed a nanoporous structure. The fluorescent

confocal microscope image of the NBD-modified fibers showed a direct proof of successful

dye-modicafication. Under 588 nm UV excitation, the fibers show strong green fluorescent emission (Figure

3.1.5F).

C D

A B

E F

Figure 3.1.5 SEM images for fibers (A, B) before and (C, D) after THF/water annealing. Optical microscope image (E) and confocal microscope image (F) of NBD dye functionalized porous Fibers. Scales, A, B, C: 10 m, D: 1 m, E and F: 100 m.

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- 33 - 161o 0o 160o H2N O NH2 2

Figure 3.1.6 Contact angle of PPFPMA-hv-PEO Fibers as electrospun and after UV irradiation, methanol washing and as 2,2'-(ethane-1,2-diylbis(oxy))diethanamine post-modification.

Electrospun polymer nanofibers films generally show superhydrophobic wetting behavior and

therefore are used in special surface applications.62 Our PEO-hv-PPFPMA fiber mats indeed showed superhydrophobic behavior with static contact angles up to 160o. However, as shown in Figure 3.1.6, the fiber mats can be transformed to superhydrophilic by simple post-modification with Jeffamine. The

measured water contact angle was zero after the fiber mats were allowed to react with

2,2'-(ethane-1,2-diylbis(oxy))diethanamine in a methanol solution at 30 oC for 12 h. FTIR indicated the reaction between the poly(FPMA) block and the amine was almost quantitative. The characteristic PFP ester band at 1780

cm-1 nearly disappeared while an imide band at 1640 cm-1 appeared (S4). This superhydrophobic to superhydrophilic transformation showed that our reactive fibers could have their properties significantly

altered by this simple modifaction procedure, while featuring a porous structure. Further exploration of

this dual porosity of fiber mats and porous fibers is currently underway.

Conclusions

In this work, photocleavable block copolymers featuring pentafluorophenyl ester moieties in one

block were obtained by RAFT polymerization. Nanoporous thin films and nanofibers were prepared

from PFP-containing photocleavble block copolymers. PFP-containing thin films and fibers show

potential for making functional materials based on activated ester-amine substitution chemistry. The

efficient post-modification of thin films and fibers was demonstrated by successful preparation of

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- 34 -

3.2 Photocleavable Triblock Copolymers Featuring

Activated Ester Middle Blocks: Synthesis and

Application as Naoporous Thin Film Templates

Introduction

Nanoporous thin films have attracted continued interest for their potential applications as

templates,45separation materials,64 and other advanced applications.65 Placing reactive functional groups on the pore walls is critically important for allowing post-modification and host-guest interactions.66 Several strategies have been developed for the fabrication of porous thin films featuring reactive pores.

Russell and coworkers reported nanoporous thin films from polystyrene-block-poly(ethylene oxide) with

a disulfide group as a junction.67 Porous structures with thiol groups on the pore surfaces were formed after D,L-dithiothreitol treatment and methanol washing. This kind of diblock copolymer with a

protected reactive junction group provided a facile method for fabricating reactive nanoporous thin films.

However, the density of the pore surface functional groups introduced by this strategy is relatively low,

which will hinder further advanced applications of the reactive thin films.

Higher density of pore surface functionality can be obtained from a triblock copolymer with a reactive

middle block. However, the synthesis of triblock copolymers with reactive middle blocks has previously

involved multiple synthetic steps, making it a synthetic challenge. For example, Hillmyer and coworkers

once used a multiple-step synthesis to prepare

polystyrene-block-poly(dimethylacrylamide)-block-polylactide, in which the midblock poly(dimethylacrylamide) was transformed to poly(acrylic acid) after

hydrolysis.53a Additionally, the reported functional groups on the pore walls in the thin films were only partially active and reacted under limited conditions. Hence, there is a strong demand for efficient and

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- 35 -

In this work, as shown in Figure 3.2.1A, a “one-step” synthesis route was developed to synthesize

photocleavable triblock copolymers with a pentaflurophenyl ester containingmiddle block. Our approach

is based on the well-known alternating copolymerization of styrene and maleimide.68 By using an excess of styrene monomer, copolymerization with a given maleimide while using a poly(ethylene oxide) (PEO)

chain transfer agent should produce a triblock copolymer with an activated ester middle block in one

step. Our triblock copolymer system has three advantages: a) “one-pot and one-step” synthesis, avoiding multiple steps of polymerization, modification and purification; b) incorporating a photocleavable

junction, an o-nitrobenzyl ester, between the PEO and poly(styrenre-co-maleimide)-b-polystyrene,

allowing the fabrication of highly-ordered nanoporous films under mild conditions,35-37 and c) the activated pentafluorophenyl ester is known to react with amines under very mild conditions, providing

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- 36 -

Figure 3.2.1 (A) Concept for “one-step” RAFT polymerization to produce reactive triblock copolymers. (B) Synthetic scheme for photocleavable triblock copolymers with a pentafluorophenyl ester middle block.

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- 37 -

Figure 3.1.2 (A) Kinetic plots for polymerization of styrene (S) in the presence of pentafluorophenyl 4-maleimidobenzoate (MAIPFP), determined by 1H NMR. (B) 1H NMR of triblock copolymer PEO-b-P(S-co-MAIPFP)-b-PS (P1) in CDCl3.

Results and Discussion

A poly(ethylene oxide) (PEO) chain transfer agent with an o-nitrobenzyl ester (ONB) junction (Macro-CTA) was synthesized by a CuAAC “click” reaction. Next, the RAFT polymerization of styrene in the presence of pentafluorophenyl 4-maleimidobenzoate (MAIPFP) and Macro-CTA was carried out in bulk at 80 °C under argon atmosphere with the ratio of [St] 0 /[ MAIPFP ]0 /[Macro-CTA]0 being 1000:12:1 (run 3 in Table 1). The polymerization kinetics was investigated by 1 H NMR measurements. The MAIPFP reached 100% conversion within 25 min, while the conversion of styrene at that time was 6%. Notably, while the polymerization rate of styrene is slow (the conversion reached around 20% after

(40)

- 38 -

16 hours), nevertheless, the polymerization was still living (Figure 3.2.2A). The polymerization kinetics

clearly demonstrate that the MAIPFP was consumed at the very early stage during the polymerization. This indicates that the MAIPFP monomer was precisely incorporated as an alternating-structure middle block between the PEO and PS blocks. The length of middle block also can be controlled by changing the ratio between MAIPFP and CTA, provided styrene is used in large excess. For example, as shown in

Figure 3.2.2B, the proton ratio between maleimide aromatic proton resonance a and the methyl ether

end group of PEO d is 10:1, which corresponds to 15 MAIPFP units in the polymer. This value of MAIPFP units is in good agreement with the feed ratio between MAIPFP and Macro-CTA, which in this case was 12:1. Other data on middle block length are summarized in Table 3.2.1.

Table 3.2.1. RAFT polymerization of styrene and MAIPFP.a

Run MAIPFP repeat unit theory MAIPFP repeat unit NMR Mnb g*mol-1 Mwb g*mol-1 Ð b 1 3 4.5 30, 300 35, 800 1.17 2 9 11.5 27, 300 32, 300 1.16 3 (P1) 12 15.1 28, 100 33, 800 1.18 4 24 34.4 30, 200 35, 000 1.20 a

Bulk, 80 oC, 15 h, styrene conversion= 18-20%, MAIPFP coversion= 100% (at 25 min) determined by 1H NMR in CDCl3.

b

GPC in THF using linear PS standards.

Photocleavage was investigated by GPC measurements. P1 (10 mg/mL in THF) in a NMR tube exposed to a UV source (6 W, 365 nm) for 12 h. In Figure 3.2.3, GPC analysis shows the complete photocleavage of P1. After UV irradiation, the elution time peak associated with the block copolymer (33,800 g./mol in GPC) split into lower molecular weight peaks (20,100 g/mol and 7000 g/mol in GPC), which were assigned as cleaved P(MAIPFP-co-S)-b-PS and PEO from P1.

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- 39 -

14

15

16

17

Elution time (min)

P

1

after UV

P

1

before UV

(42)

- 40 - 0.2 0.4 0.6 0.8 1.0 v7 v4 v3 In te n s it y ( a .u .) qy (nm-1) 1

C

Figure 3.2.4 (A) AFM image for P1 thin film after water/THF annealing for 2.5 hours. (B) 2D GISAXS pattern for P1 thin film. (C) Intensity scans along qy of the GISAXS patterns.

A 35 nm thick BCP thin film was prepared by spin-coating a solution of 0.8 wt % of P1 in toluene

onto silicon substrates. Subsequently, the film was annealed in a THF/water vapor environment. The

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- 41 -

shown in Figure 3.2.4A. The highly ordered hexagonally packed arrays indicated that PEO cylinders

were oriented normal to the substrate. Further, the static grazing incidence small-angle X-ray scattering

(GISAXS) was used to characterize the thin films over a large area. An incidence angle of 0.2o, which is between the critical angle of polymer (0.16o) and silicon substrate (0.28o), was chosen so that the X-ray can penetrate into the film, where the scattering profiles are characteristic for the entire film. The corresponding 2D GISAXS pattern is shown in Figure 3.2.4B, in which, qy represented the momentum transferred normal to the

incident plane, i.e. parallel to the thin film surface while qz is normal to the sample surface. Brag rods

(reflections extended along qz) were seen, which was characteristic of cylindrical microdomains oriented

normal to the film surface. The observed multiple order reflection peaks are characteristic of long-range

ordering. A line scan in qy is shown in Figure 3.2.4C. The first order reflection was at q* = 0.205 nm-1

and the d spacing (d = 2π/q*) was calculated to be 31 nm. Highly-ordered nanoporous thin films were

formed after UV exposure and a successive methanol wash to selectively remove the PEO block. As can

be seen from TEM images in Figure 3.2.5A, the nanoporous morphology is clear without need for any

staining due to the large difference in electron density between the matrix and the empty pores. An

average pore diameter of 16 nm and an average center-to-center distance between the pores of 35 nm

were obtained, which is in good agreement with the GISAXS data.

A

B

C

Figure 3.2.5. (A) TEM image of the nanoporous thin film from P1 after UV treatment and methanol wash, scale: 70 nm. (B) AFM phase image for iron oxide nanodots. (C) AFM height image for iron oxide nanodots. Scale for B and C: 2 m x 2 m.

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- 42 -

To confirm the presence of reactive functional groups on the pore walls, the nanoporous film was

immersed into a solution of 2-aminoethyl-ferrocene (Fc-amine) in ethanol, anchoring Fc-amine to the

pore walls via the activated esters. The modified nanoporous films were then treated with oxygen

plasma to remove the organics and convert Fc to iron oxide (Figure 3.2.5B and C). If, as we

hypothesize, the reactive ester groups are located at the pore walls, iron oxide nanoring patterns should

result. However, out of our expectation, as is shown in Figure 3.2.5B and C, we observed highly ordered

nanodots with a diameter of around 20 nm. To explore the origin of nanodots formation rather than

nanorings, TEM images were taken after Fc-amine modification and washing with methanol. As shown

in Figure 3.2.6A, the Fc-amine appears to have aggregated in the center of the open pores rather than

decorating the pore walls. This could be the result of unfavorable interactions between the hydrophilic

Fc-amine and the hydrophobic pore walls. The aggregated Fc-amine can be removed after immersing the

thin film into HCl solution (concentration: 0.1 M) for 3 hours (Figure 3.2.6B). However, no nanotorus

was observed in the TEM after acid washing step. The electron density contrast between the Fc-amine

functionalized pore walls and the PS matrix may not be sufficient enough to observe this sub-10 nm

feature.

Figure 3.2.6 (A) TEM image of nanoporous P1 thin film after UV irradiation, Fc-amine post-modification, and methanol wash, scale: 70 nm. (B) TEM image for sample in Figure 3.2.6A after acid wash.

Finally, the sample as shown in Figure 3.2.6B was treatment with oxygen plasma, during which

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- 43 -

morphology is shown in Figure 3.2.7. The average diameter of the torus was around 39 nm and their

average height was around 1 nm. The torus had a minor radius 3.5 nm and a major radius 16 nm. These

structures result from the activated esters located at the interface of the copolymer films that are exposed

after PEO removal. The structure of the donuts supports our assertion that the alternating

styrene-maleimide served a middle block between PEO and PS.

The resulting nanodonuts were further characterized by high resolution X-Ray photoelectron spectroscopy (XPS). The results are shown in Figure 3.2.7D. Two binding peaks can be seen at 725 and 710 eV, which were assigned to Fe 2p and Fe 2p1/2 in a -Fe2O3 sample, respectively. The XPS

measurement once again demonstrates that we successfully postmodified the thin films with Fc-amine.

Figure 3.2.7 (A, B) AFM height images for iron oxide donuts. Scales: A, 2 m x 2 m; B 0.5 m x 0.5 m. (C) Height profile in B, height scale is 2 nm. (D) High resolution XPS for sample shown in Figure 6A.

Conclusion.

In conclusion, we have demonstrated that activated ester-functionalized nanopores can be generated

from photocleavable block copolymers with an activated ester middle block. The functionalities at the

interface between the matrix and pore walls can then be used as handles to generate iron oxide

nanodonuts. The results in this work present a unique example of a mild etching process and interface

functionalization based on o-nirtrobenzyl ester and activated ester chemistries. The method described

here provides a broad range of possibilities, because the activated esters are reactive towards a large

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- 44 -

3.3

-Photolabile Amine Semitelechelic Polymers

for Light-induced Macromolecular Conjugation

Introduction

Increasing attention has been paid to block copolymers and biological/synthetic hybrid materials,

causing a variety of strategies to be developed for synthesizing these materials using a macromolecular

conjugation approach. Examples of these syntheses include copper catalyzed azide-alkyne cycloaddition

(CuAAC),70 thiol-ene and thiol-yne chemistries,71, 72 oxime formation,73 Diels–Alder cycloaddition,74 and the reaction of activated esters with amines.69 Among conjugation approaches, UV light-induced macromolecular conjugation or surface-conjugation has attracted great interest as it can provide spatial

and temporal control over these reactions that are not available to other chemistries. Until now,

photo-triggered thiol-ene/yne has been explored by several groups.75 Popik and coworkers reported selective labeling of living cells based on photo triggered acetylene-azide cycloaddition.76 Barner-Kowollik and coworkers introduced UV light-induced Diels–Alder reactions for preparation of block copolymers and

photo-patterning.77

Activated ester-amine chemistry has many features of more conventional “click” chemistries, featuring

metal free, mild condition reactions and a practically quantitative conversion. It has found wide

application, including in peptide synthesis and preparation of well-defined reactive polymers and

bio-hybrids.78 However, there are only a few reports about light-triggered activated ester-amine chemistry, which would provide more spatial and temporal control about macromolecular conjugation. Recently,

based on activated ester-amine chemistry, we synthesized a photolabile amine that can be successfully used for the preparation of reactive photopatternings.79 These previous results encouraged us to develop a macromolecular conjugation chemistry based on this phototriggered activated ester-amine chemistry. In this work, we report an-photolabile amine semitelechelic polymer that can be used for macromolecular conjugation based on light triggered activated ester-amine chemistry.

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- 45 -

Results and Discussion

NO2 O O O N N S O O CN S O N N S O O O S 2 NC O O NO2 O O NO2 O O O N NH O NO2 O O O Cl O HN NH NaCO3, H2O/Dioxane 60% 5 eq. 1 eq. S O CN S O F F F F F 1 eq. lutidine, rt, 12h 80% 0oC 1h, rt 18 h O O O 2 AIBN (0.1 eq.) 70oC, 15h 1 2 3 hv-POEGMA O N N O O O 2 NC O O NO2 O O hv-POEGMA N N O O O 2 NC O O PS-POEGMA NO O O CHO CO2 + CN N N O O O 2 NC O CN H CN Br O Br O F F F F F

Scheme 3.3.1 Synthesis of photolabile amine CTA (1) andhv-POEGMA.

Polymer Synthesis. Well-defined telechelic polymers featuring activated ester end groups have been

previously studied.69 The goal of our synthetic strategy was to place a photolabile amine at the end group of the polymer chain to enable a photo-triggered activated ester-amine conjugation. As shown in

Scheme 3.3.1, an o-nitrobenzyl (ONB) protected amine functionalized chain transfer agent (1) was

synthesized in two steps with a yield of around 50% (see experimental section for synthesis details).

First the ONB mono-protected diamine (2) was synthesized via a one step reaction. Then the ONB

protected amine CTA (1) was prepared by reaction of compound 2 with PFP-CTA under mild

conditions. The CTA(1) was then successfully employed in the mediation of the RAFT polymerization

of diethylene glycol methyl ether methacrylate (DEGMA) was mediated by CTA 1 in dioxane at 80 oC (Scheme 3.3.1). The kinetics of RAFT polymerization of DEGMA using CTA 1 are shown in Figure

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- 46 -

NMR) and time. After 4 hours, the monomer conversion reached about 40%. Additionally, the kinetics

of polymerization were also examined by GPC. The molecular weight (Mn) measured by GPC increased

linearly with time, with corresponding Ð between 1.25 and 1.30 over the course of the reaction.Both the kinetic plots and low Ð confirm that the polymerizaion follows controlled radical polymerization chareacteriscs. The final polymer was purified by precipitation from n-hexane, and the 1H NMR spectrum of the purified homopolymer is provided in Figure 3.3.2. As already shown in our previous studies,

ONB of CTA normally remained intact after RAFT polymerization.37 In Figure 3.3.2, the proton C was assigned to the resonance of end group ONB, which was clearly observed. The ratio between

resonances C and B (phenyl from CTA) was aound 1.15: 1.0. Therefore, we believe that the majority of

ONB groups remained intact after RAFT polymerization.

1.0

1.2

1.4

1.6

1.8

2.0

0

10

20

30

40

50

0

10

20

30

40

50

Ð

Conversion

M

n

/

1

0

3

g

*m

o

l

-1

Figure 3.3.1 Kinetics of DEGMA RAFT polymerization as mediated by CTA 1 in dioxane at 80 oC. Mn

(49)

- 47 - 8 7 6 5 4 3 2 1 0 k

*

*

*

j j i h g f e E B C A d c b b a NO2 O O O N N S O O CN S a c

*

d A C B E e, f g, h i k 90.30 O N N S O O O S 2 NC O O NO2 O O

ppm

2.00

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- 48 -

Photolysis of Polymer with Photolabile Amine. Photolysis of the photolabile amine containing

polymer was investigated by 1H NMR and UV-Vis spectroscopy. Generally, CTA end group tend to react with amines, yielding thiol groups via an aminolysation. To avoid this side reaction, CTA end

group was removed via treatment with an excess AIBN (ca. 30 equiv.) to the polymer P0 in dioxane

under 80 oC. As shown in Figure 3.3.2, the resonance at 7.72-7.36 ppm assigned to the aromatic group of the CTA end group disappeared completely (Figure 3.3.2), which indicated quantitative removal of

the CTA end group. However, the resonances a, b and c assigned to the typical protons of the ONB

protecting group 81 were still observed after end group removal. Next, the photolysis reaction of the polymer P0 in THF (ca. 30 mg/ml) was carried out in a NMR tube. The solution was irradiated using a

UV lamp (6 W, wavelength = 365 nm) for 12 hours at room temperature. After the UV irradiation, the

solution became deep yellow, which was the result of the formation of the o-nitrosobenzyl

compound.82The final product was purified by precipitating the crude solution from n-hexane three times. As shown in Figure 3.3.2, the proton resonance a, b and c in P1 had completely disappeared,

which indicated the complete removal of ONB protecting group. In early reports about ONB protected

amines, there is often a side reaction81 between the coproduct o-nitrosobenzadyhe and released amine. However, in our case, the released amine is a secondary amine, which is a poor substrate for this side

reaction. There are no aromatic resonances in the 1H NMR of P2, which further supports that the released amine did not react with o-nitrosobenzadyhe. The photolysis reaction was also investigated by

UV-Vis spectroscopy. The photocleavage of ONB proceeded rapidly under a high intensity 500 W UV

source (= 365 nm), with complete photolysis within 30 min. As shown in Figure 3.3.3, the absorption intensity at 343 nm (associated with the o-nitrobenzyl moiety) decreased with increasing irradiation UV

time. At the same time, additional peak appeared between 356 and 450 nm as the result of the formation

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- 49 -

8

7

6

5

4

3

2

1

0

P2

P1

c

c

b

a

a

P2

NH N O O O 2 NC O CN O N N O O O 2 NC O O N O2 O O CN

ppm

P1

b

UV 365 nm

(52)

- 50 - 300 400 500 0.0 0.2 0.4 NO2 O O O N O NO O O O = 365 nm Time/min 0 1 3 5 10 20 30 40 A b s . Wavelength (nm)

Figure 3.3.2. UV irradiation time dependent UV-Vis spectra of P1 in THF (concentration: 0.02 mg/mL).

Macromolecular Conjugation. As shown in Scheme 3.3.2, macromolecular conjugation proceeded in

two steps. First, photolysis of P1 generated the free amine functionalized P2, followed by conjugation of

P2 to a PFP end functionalized polystyrene. A hydrophobic polystyrene was chosen as a the

corresponding conjugation block, in order to simply purification and characterization of the obtained

diblock copolymer.

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15 In order to explicitly investigate structure formation process in block copolymer melts, we will introduce a particle-based model and numerical methods to solve this model in

In addition, in order to develop more functional amphiphilic block copolymers, another two types of copolymers, grafted poly(2-methyl-2-

length of the worm/rod-like micelles of about 400 nm. This is shorter than what is observed in TEM. In here worms/rods can be found which are longer than 1 µm. But the model used for

28, 29 As a model we synthesized poly(2-hydroxyethyl methacrylate)-co-poly(n-butyl methacrylate)-co-poly(2-hydroxyethyl methacrylate) (PHEMA-co-PBMA-co-PHEMA) block copolymers